Myocardial infarction, which is caused by myocardial necrosis brought about by coronary artery occlusion, is an important issue to be solved in clinical medicine since it causes sudden cardiac death and chronic cardiac death. In the case of acute myocardial infarction in particular, the mortality rate is high at 35% to 50%, and 60% to 70% of fatal cases die within 1 to 2 hours after the attack. In addition, even if patients survive the acute stage, in cases in which the myocardial necrotic lesion is large following the initial attack, there is a high risk of succumbing to recurrent myocardial infarction or accompanying heart failure. Thus, in treating myocardial infarction, it is necessary to rapidly implement treatment soon after the attack has occurred, and it is important to minimize the size of the necrotized myocardium, namely the infarct size, as much as possible.
For example, in myocardial infarctions such as severe massive myocardial infarction, since left ventricular remodeling proceeds leading to heart failure, prognosis is known to be poor. In general, coronary recanalization therapy in the form of thrombolytic therapy or revascularization is typically performed for myocardial infarction. However, there are many cases in which the effects of recanalization may not be obtained or conversely, myocardial cells may be damaged by reperfusion injury and the like, and satisfactory therapeutic effects may not be obtained by recanalization therapy alone. Consequently, although studies have been conducted on pharmaceutical agents expected to demonstrate myocardial protective action for use as an adjuvant therapy to recanalization therapy, a satisfactory pharmaceutical agent has yet to be found. In addition, in the case of serious massive myocardial infarction, prognosis would improve if it were possible to regenerate necrotic myocardial tissue and improve left ventricular remodeling. However, there is currently no medical treatment that is effective against the aforementioned disorders.
As was previously described, in the treatment of myocardial infarction, although it is required to rapidly provide treatment soon after an attack, since there is no definitive treatment method for minimizing infarct size, efforts are being focused on regenerating the myocardial tissue that has necrotized. In particular, attention has recently been focused on biological cells capable of contributing to tissue regeneration. Although known examples of cells obtained from adults that have the ability to differentiate include mesenchymal stem cells (MSC) that have the ability to differentiate into bone, cartilage, adipocytes, neurons or skeletal muscle and the like (Non-Patent Documents 1 and 2), these consist of cell groups containing various cells, the actual state of their ability to differentiate is not understood, and there have been considerable fluctuations in therapeutic effects. In addition, although iPS cells (Patent Document 1) have been reported to be adult-derived pluripotent stem cells, in addition to the establishment of iPS cells requiring an extremely complex procedure involving the introduction of specific genes into mesenchymal cells in the form of a skin fibroblast fraction and the introduction of specific compounds into somatic cells, since iPS cells have a high tumorigenic potential, extremely high hurdles must be overcome for their clinical application.
It has been determined from research by M. Dezawa, one of the inventors of the present invention, that multilineage-differentiating stress enduring cells (Muse cells) expressing surface antigen in the form of stage-specific embryonic antigen-3 (SSEA-3), which are present in mesenchymal cell fractions and can be obtained without going through an induction procedure, are responsible for the pluripotency possessed by mesenchymal cell fractions, and that they have the potential for application to disease treatment aimed at tissue regeneration. In addition, Muse cells were also determined to be able to be concentrated by stimulating mesenchymal cell fractions with various types of stress (Patent Document 2, Patent Document 3). However, there have yet to be any examples of the use of Muse cells for the prevention and/or treatment of myocardial infarction such as serious massive myocardial infarction or its accompanying heart failure, and the obtaining of anticipated therapeutic effects has yet to be clearly determined.